1. Field of the Invention
This invention relates to compositions and methods for releasing active agents at a selected rate. More particularly, this invention relates to such methods and compositions using inorganic microtubular ceramics, and especially naturally occurring microtubular minerals for environmentally friendly controlled release.
2. Description of the Related Art
Active agents are chemicals that have some effect in some environment of use. For almost any active agent, for use in almost any use environment, it is desired to modulate the release of the active agent into the use environment, so that the active agent is released into the use environment at a selected rate, and over a selected time. There are several, frequently complementary, reasons for modulating active agent release.
Many active agents are preferably released at a desired concentration, or in a desired concentration range. Drugs, for example, are preferably introduced into the body within a therapeutic range. Below this range, there will not be enough of the drug in the body to achieve the desired therapeutic effect. Above this range, no additional therapeutic effect will be conferred, or adverse side effects of the drug will outweigh the therapeutic effect of the drug.
Analogous dynamics are at work for most every active agent. As another example, antifouling agents for use on ship hulls are typically environmentally unfriendly. Thus, it is desired to control the release rate of these antifouling agents, to keep their release into the environment at an acceptable level. At the same time, it is desired to release these antifouling agents at effective levels. See generally U.S. Pat. No. 5,049,382, issued Sep. 17, 1991 to Price et al.
Likewise, many active agents are preferably released at a sustained rate over a desirable period. For example, many drugs (e.g., antibiotics) are preferably absorbed and metabolized by the body over a prolonged therapeutic course of treatment. Traditionally, this is done by administering repeated, regular doses (e.g., regular oral or injected doses), or by a sustained administration, such as an intravenous drip. Other drugs (e.g., antihypertensive drugs, birth control hormones) do not have a finite course of treatment. For these drugs, sustained controlled delivery is a matter of convenience and an assurance against a lapse of memory.
Sustained delivery is also desired for many other active agents. For antifouling agents, it is highly desirable to sustain delivery of an effective amount of the antifouling agent for as long as possible, to maximize the time between applications of the agent. For pesticides, pheromones, and other active agents used to control pest populations, sustained delivery of these agents for at least the duration of a growth or reproduction cycle is highly desirable. See generally U.S. Pat. No. 4,017,303, issued April 12, 1977 to Coplan et al.
For these and other types of active agents, several concerns present themselves. It is generally desirable to release an active agent at a controlled rate, to maintain a constant level of the active agent. Unfortunately, many of the systems used for the modulated delivery of active agents do not release these active agents at a controlled rate. Systems using layered structures that ablade or dissolve one layer at a time tend to release their active agents in cycles, with the levels of active agents oscillating between highs and lows.
Liposomal tubules and other microstructures, which have been proposed for use in a system for the modulated delivery of an active agent, (see Price et al., supra) have several shortcomings. These tubules must be manufactured: they do not occur naturally. They release their entrapped contents very quickly, over a time scale of minutes. They do not inherently permit a low solubility active agent to be readily introduced into a use environment, at a desired effective rate, such as effectively delivering a hydrophobic active agent in vivo. However, liposome tubules do have several advantages: they are small enough to be injected or to be incorporated in a coating such as an antifouling paint, and they have broad applicability to a range of active agents and use environments.
Metal tubules and other microstructures have also been proposed for use in the modulated release of an active agent. These metal structures typically are made by metallizing a lipid microstructure. In addition to the additional processing and cost concerns inherent to metallized tubules, there is the additional environmental unfriendliness associated with many metals used in these applications (e.g., copper).
Polymers and other carriers are sometimes used for the modulated release of an active agent that has at least some solubility in these carriers. In these applications, the active agent is mixed with the carrier, to dissolve the active agent in the carrier. As the active agent diffuses through the carrier to the interface of the carrier and the use environment, the active agent is released into the use environment. Typical examples of such systems are flea and tick collars for pets. Unfortunately, many active agents have undesirably low solubility in many of the available carriers. A consequence of this low solubility is that in many instances, the delivery system will contain only an undesirably small amount of the active agent, limiting the useful life of the delivery system. For example, flea and tick collars for pets have undesirably short useful lives, shorter than the flea and tick seasons in many parts of the country. A delivery system that would permit the inclusion of a larger volume of active agent in a delivery system is desired. Also, many of these polymers used in modulated release applications are environmentally unfriendly.